TY - JOUR
T1 - Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress
T2 - Possible involvement of oxygen free radicals
AU - Bates, Brian
AU - Hirt, Lorenz
AU - Thomas, Sunu S.
AU - Akbarian, Schahram
AU - Le, Dean
AU - Amin-Hanjani, Sepideh
AU - Whalen, Michael
AU - Jaenisch, Rudolf
AU - Moskowitz, Michael A.
N1 - Funding Information:
The authors thank Margarita Behrens for help in setting up the cell culture system, Jessica Daussmann and Ruth Flannery for animal support, Jeanne Reis for histology, and Nick Plesnila and Cindy Chen for technical help. The authors also thank Margarita Behrens and Dennis Choi for communicating unpublished results and Kuo Fen Lee for providing reagents. We also thank Margarita Behrens, Maribel Rios, Paul Yaworsky, and Seung Kwak for critical reading of the manuscript. This work was supported by Schweizerische Stiftung fuer Medizinisch Biologische Stipendien and the Foundation SICPA for fellowships to L.H.; Cure Autism Now Foundation Fellowship to S.A.; NIH Grant 5-R350CA44339 to R.J.; and NIH-Interdepartmental Stroke Program Project Grant 5-P50NS10828.
PY - 2002
Y1 - 2002
N2 - To explore the role of neurotrophin-3 (NT-3) during cerebral ischemia, NT-3-deficient brains were subjected to transient focal ischemia. Conditional mutant brains produced undetectable amounts of NT-3 mRNA, whereas the expression of the neurotrophin, BDNF, the NT-3 receptor, TrkC, and the nonselective, low-affinity neurotrophin receptor p75NTR, were comparable to wild-type. Baseline absolute blood flow, vascular and neuroanatomical features, as well as physiological measurements were also indistinguishable from wild-type. Interestingly, the absence of NT-3 led to a significantly decreased infarct volume 23 h after middle cerebral artery occlusion. Consistent with this, the addition of NT-3 to primary cortical cell cultures exacerbated neuronal death caused by oxygen-glucose deprivation. Coincubation with the oxygen free radical chelator, trolox, diminished potentiation of neuronal death. NT-3 also enhanced neuronal cell death and the production of reactive oxygen species caused by oxidative damage inducing agents. We conclude that endogenous NT-3 enhanced neuronal injury during acute stroke, possible by increasing oxygen-radical mediated cell death.
AB - To explore the role of neurotrophin-3 (NT-3) during cerebral ischemia, NT-3-deficient brains were subjected to transient focal ischemia. Conditional mutant brains produced undetectable amounts of NT-3 mRNA, whereas the expression of the neurotrophin, BDNF, the NT-3 receptor, TrkC, and the nonselective, low-affinity neurotrophin receptor p75NTR, were comparable to wild-type. Baseline absolute blood flow, vascular and neuroanatomical features, as well as physiological measurements were also indistinguishable from wild-type. Interestingly, the absence of NT-3 led to a significantly decreased infarct volume 23 h after middle cerebral artery occlusion. Consistent with this, the addition of NT-3 to primary cortical cell cultures exacerbated neuronal death caused by oxygen-glucose deprivation. Coincubation with the oxygen free radical chelator, trolox, diminished potentiation of neuronal death. NT-3 also enhanced neuronal cell death and the production of reactive oxygen species caused by oxidative damage inducing agents. We conclude that endogenous NT-3 enhanced neuronal injury during acute stroke, possible by increasing oxygen-radical mediated cell death.
UR - https://www.scopus.com/pages/publications/0036183202
U2 - 10.1006/nbdi.2001.0458
DO - 10.1006/nbdi.2001.0458
M3 - Article
AN - SCOPUS:0036183202
SN - 0969-9961
VL - 9
SP - 24
EP - 37
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -